BACKGROUND: Dendritic cells (DCs) generated from leukemic blasts constitute a promising tool in immunotherapy for acute myeloid leukemia patients (AML-DCs), because AML-DCs express human leukocyte antigens and costimulatory molecules such as CD40, CD80, and CD86 at a higher level than leukemic blasts. Potentiation of AML-DC vaccine might become feasible by the addition of adjuvants such as lipopolysaccharides (LPS) or CPG-rich oligodeoxyribonucleotides binding to Toll-like receptors (TLR) and inducing a stronger Type 1 T-cell response. STUDY DESIGN AND METHODS: mRNA and protein expression of TLR-2, -4, and -9 were analyzed with quantitative real-time polymerase chain reaction, Western blot, and flow cytometry for mature monocyte-derived DCs generated from 14 AML patients versus 14 healthy volunteers (HV-DCs), and the response of the AML- and HV-DCs to different microbial TLR ligands was determined by enzyme-linked immunosorbent assay for the proinflammatory cytokines tumor necrosis factor (TNF)-alpha, inducible protein (Ip)-10, and interleukin (IL)-6. RESULTS: AML-DCs and HV-DCs strongly expressed TLR-2 and TLR-4, while TLR-9 was expressed at a lower level in both groups. There was no significant difference in TLR expression between the two groups of AML-DCs and HV-DCs. In accordance with the TLR expression levels, DCs generated from both AML patients and HVs responded to the known microbial ligands peptidoglycan (PGN) and lipoteichoic acid for TLR-2 and LPS as ligand for TLR-4, by producing TNF-alpha and IL-6. A response to the ODNs 2006 and 2216 binding to TLR-9 was only detected in AML-DCs. CONCLUSION: Microbial ligands like ODNs and LPS constitute promising adjuvants for enhancing (AML-) DC vaccines.
BACKGROUND: Dendritic cells (DCs) generated from leukemic blasts constitute a promising tool in immunotherapy for acute myeloid leukemiapatients (AML-DCs), because AML-DCs express human leukocyte antigens and costimulatory molecules such as CD40, CD80, and CD86 at a higher level than leukemic blasts. Potentiation of AML-DC vaccine might become feasible by the addition of adjuvants such as lipopolysaccharides (LPS) or CPG-rich oligodeoxyribonucleotides binding to Toll-like receptors (TLR) and inducing a stronger Type 1 T-cell response. STUDY DESIGN AND METHODS: mRNA and protein expression of TLR-2, -4, and -9 were analyzed with quantitative real-time polymerase chain reaction, Western blot, and flow cytometry for mature monocyte-derived DCs generated from 14 AMLpatients versus 14 healthy volunteers (HV-DCs), and the response of the AML- and HV-DCs to different microbial TLR ligands was determined by enzyme-linked immunosorbent assay for the proinflammatory cytokines tumor necrosis factor (TNF)-alpha, inducible protein (Ip)-10, and interleukin (IL)-6. RESULTS:AML-DCs and HV-DCs strongly expressed TLR-2 and TLR-4, while TLR-9 was expressed at a lower level in both groups. There was no significant difference in TLR expression between the two groups of AML-DCs and HV-DCs. In accordance with the TLR expression levels, DCs generated from both AMLpatients and HVs responded to the known microbial ligands peptidoglycan (PGN) and lipoteichoic acid for TLR-2 and LPS as ligand for TLR-4, by producing TNF-alpha and IL-6. A response to the ODNs 2006 and 2216 binding to TLR-9 was only detected in AML-DCs. CONCLUSION: Microbial ligands like ODNs and LPS constitute promising adjuvants for enhancing (AML-) DC vaccines.
Authors: RuiKun Zhong; Hongying Li; Karen Messer; Thomas A Lane; Jiehua Zhou; Edward D Ball Journal: Cancer Immunol Immunother Date: 2015-03-21 Impact factor: 6.968
Authors: Ulf Schnetzke; Mike Fischer; Anne-Kathrin Kuhn; Bärbel Spies-Weisshart; Elisabeth Zirm; Andreas Hochhaus; Jörg P Müller; Sebastian Scholl Journal: J Cancer Res Clin Oncol Date: 2012-12-21 Impact factor: 4.553
Authors: Dragana Nikitovic; Maria Tzardi; Aikaterini Berdiaki; Aristidis Tsatsakis; George N Tzanakakis Journal: Front Immunol Date: 2015-04-14 Impact factor: 7.561